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1.
Biomed Res Int ; 2022: 9911472, 2022.
Article in English | MEDLINE | ID: mdl-35281615

ABSTRACT

Background: Endometriosis (EMs) is a benign chronic condition that tends to recur in women of childbearing age, with an incidence of approximately 10%. It is a multifactorial disease for which the pathogenesis is currently unclear. This study is aimed at investigating the expression and clinical significance of tRNA-derived small RNA (tsRNA), a novel noncoding small RNA with potential regulatory functions, in endometriosis. Methods: The tRF/tiRNA expression profiles in endometrial tissues from three pairs of endometriosis patients and controls were detected by tRF&tiRNA PCR microarray technology and then verified by quantitative real-time polymerase chain reaction (qPCR). The target genes and target sites of TRF396, tiRNA-5030-GlnTTG-3, TRF308, and TRF320 were predicted by miRanda, and the network diagram of their interaction with miRNA was drawn. The impact of tRNA-derived fragments on the pathogenesis of endometriosis was analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: Two upregulated and 19 downregulated tRNA-derived fragments were identified. The qRT-PCR results of 2 upregulated and 2 downregulated RNA-derived fragments were consistent with the RNA Seq data. The OR2B4 gene related to TRF396, the DGAT1 gene related to tiRNA-5030-GlnTTG-3, the KLF16 gene of TRF308, and the RNF213 gene of TRF320 had significant correlations. Gene Ontology and pathway analysis showed that the target genes of TRF396 and tiRNA-5030-GlnTTG-3 were mainly involved in the intrinsic components of the membrane and the overall composition of the membrane in cell components; molecular functions mainly involve olfactory conduction and G protein-coupled receptor activity. In the biological process, it was mainly involved in the detection of sensory stimuli. The target genes of TRF308 and TRF320 were mainly involved in the intracellular part; molecular functions are mainly related to DNA binding transcription factor activity and protein binding and mainly related to biological regulation of biological processes. Pathway analysis showed that the RAP1 signaling pathway and the AXON GUIDANCE signaling pathway may participate in the progression of endometriosis. Conclusion: The differential expression of tRF/tiRNA in endometriosis may be related to the pathogenesis of endometriosis. Furthermore, tRF/tiRNA may be a biomarker for the diagnosis and treatment of EMs in the future.


Subject(s)
Endometriosis , MicroRNAs , Adenosine Triphosphatases , Computational Biology , Endometriosis/pathology , Female , Gene Ontology , Humans , Kruppel-Like Transcription Factors , MicroRNAs/genetics , RNA, Transfer/genetics , RNA, Transfer/metabolism , Ubiquitin-Protein Ligases
3.
Oncol Lett ; 12(6): 4403-4410, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28105153

ABSTRACT

As an integral component of the surgical staging system, lymphadenectomy for patients with endometrial cancer (EC) remains controversial, particularly in clinical stage I disease that includes not only low-risk, but also high-risk subgroups. In order to maximize the therapeutic effect of lymph node excision for high-risk patients who can potentially obtain survival benefits from it while minimizing its reverse effects in low-risk patients, pre-operative risk stratification of lymph node metastasis is necessary. The upregulation of microRNA-205 (miR-205) in carcinoma of the endometrium has been consistently reported recently and has been found to correlate with poor survival. The current study aimed to investigate whether the overexpression of miR-205 in curettage samples of EC could identify patients who are at a high risk for lymph node metastasis prior to surgery and validate the role of miR-205 as a prognostic marker in EC. Relative quantification detection of miR-205 in curettage and hysterectomy specimens of patients with EC was performed. Prediction of lymph node metastasis based on miR-205 expression, as well as tumor type and grade in curettage samples, was performed for all EC patients and patients with clinical stage I disease. Moreover, survival analysis was conducted. It was observed that miR-205 was significantly and consistently elevated in the curettage and hysterectomy samples of EC relative to normal controls. Furthermore, the overexpression of miR-205 could predict lymph node metastasis with a high accuracy and was revealed again to be associated with a poor prognosis in EC. Prospective and multicentric studies are required to further clarify the value of miR-205 as a promising predictor to stratify risk for lymph node metastasis in EC.

4.
Drug Des Devel Ther ; 9: 425-64, 2015.
Article in English | MEDLINE | ID: mdl-25624750

ABSTRACT

Ovarian cancer is a leading killer of women, and no cure for advanced ovarian cancer is available. Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects, and is under clinical investigation for the treatment of advanced solid tumor and hematologic malignancies. However, the role of ALS in the treatment of ovarian cancer remains unclear. This study investigated the effects of ALS on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT), and the underlying mechanisms in human epithelial ovarian cancer SKOV3 and OVCAR4 cells. Our docking study showed that ALS, MLN8054, and VX-680 preferentially bound to AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking. ALS had potent growth-inhibitory, proapoptotic, proautophagic, and EMT-inhibitory effects on SKOV3 and OVCAR4 cells. ALS arrested SKOV3 and OVCAR4 cells in G2/M phase and induced mitochondria-mediated apoptosis and autophagy in both SKOV3 and OVCAR4 cell lines in a concentration-dependent manner. ALS suppressed phosphatidylinositol 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways but activated 5'-AMP-dependent kinase, as indicated by their altered phosphorylation, contributing to the proautophagic activity of ALS. Modulation of autophagy altered basal and ALS-induced apoptosis in SKOV3 and OVCAR4 cells. Further, ALS suppressed the EMT-like phenotype in both cell lines by restoring the balance between E-cadherin and N-cadherin. ALS downregulated sirtuin 1 and pre-B cell colony enhancing factor (PBEF/visfatin) expression levels and inhibited phosphorylation of AURKA in both cell lines. These findings indicate that ALS blocks the cell cycle by G2/M phase arrest and promotes cellular apoptosis and autophagy, but inhibits EMT via phosphatidylinositol 3-kinase/Akt/mTOR-mediated and sirtuin 1-mediated pathways in human epithelial ovarian cancer cells. Further studies are warranted to validate the efficacy and safety of ALS in the treatment of ovarian cancer.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Aurora Kinase A/antagonists & inhibitors , Autophagy/drug effects , Azepines/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Neoplasms, Glandular and Epithelial/enzymology , Ovarian Neoplasms/enzymology , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Aurora Kinase A/chemistry , Aurora Kinase A/metabolism , Azepines/chemistry , Azepines/metabolism , Binding Sites , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Female , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , Hydrogen Bonding , Molecular Docking Simulation , Molecular Structure , Molecular Targeted Therapy , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Phosphatidylinositol 3-Kinase/metabolism , Protein Binding , Protein Conformation , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Pyrimidines/chemistry , Pyrimidines/metabolism , Signal Transduction/drug effects , Sirtuin 1/metabolism , TOR Serine-Threonine Kinases/metabolism , Time Factors
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